COVID-19 opens the door for right iliac fossa pain treatment pathway.

INTRODUCTION: The COVID-19 pandemic has increased the risks of surgery and management of common surgical conditions has changed, with greater reliance on imaging and conservative management. The negative appendectomy rate (NAR) in the UK has previously remained high. The aim of this study was to quantify pandemic-related changes in the management of patients with suspected appendicitis, including the NAR. METHODS: A retrospective study was performed at a single high volume centre of consecutive patients aged over five years presenting to general surgery with right iliac fossa pain in two study periods: for two months before lockdown and for four months after lockdown. Pregnant patients and those with previous appendectomy, including right colonic resection, were excluded. Demographic, clinical, imaging and histological data were captured, and risk scores were calculated, stratifying patients into higher and lower risk groups. Data were analysed by age, sex and risk subgroups. RESULTS: The mean number of daily referrals with right iliac fossa pain or suspected appendicitis reduced significantly between the study periods, from 2.92 before lockdown to 2.07 after lockdown (p<0.001). Preoperative computed tomography (CT) rates increased significantly from 22.9% to 37.2% (p=0.002). The NAR did not change significantly between study periods (25.5% prior to lockdown, 11.1% following lockdown, p=0.159). Twelve (75%) out of sixteen negative appendectomies were observed in higher risk patients aged 16-45 years who did not undergo preoperative CT. The NAR in patients undergoing CT was 0%. CONCLUSIONS: Greater use of preoperative CT should be considered in risk stratified patients in order to reduce the NAR.

Molecular cloning of the cDNA encoding the carboxy-terminal domain of chimpanzee apolipoprotein(a): an Asp57 --> Asn mutation in kringle IV-10 is associated with poor fibrin binding.

Insight into the structural features of human lipoprotein(a) [Lp(a)] which underlie its functional implication in fibrinolysis may be gained from comparative studies of apo(a). Indeed, cloning of rhesus monkey apo(a) has shown that a Trp72 --> Arg mutation in the lysine-binding site (LBS) of KIV-10 leads to loss of lysine-binding properties of the rhesus Lp(a) particle. Consequently, comparative studies of apo(a) sequences in different Old World monkey species should further our understanding of the molecular role of Lp(a) in the fibrinolytic process. In contrast to other Old World monkeys, including rhesus monkey, cynomolgus, and baboon, the chimpanzee exhibits an elevated level of Lp(a) and a distinct isoform distribution as compared to humans [Doucet et al. J. Lipid Res. (1994) 35, 263-270]. Clearly then, the chimpanzee is an interesting animal model for study of the structure, function, and potential pathophysiological roles of Lp(a). We have cloned and sequenced the region of chimpanzee apo(a) cDNA spanning KIV-3 to the stop codon. The global organization of this region is similar to that of human apo(a) with the presence of KV, which is absent in rhesus monkey apo(a). Nucleotide sequence comparison indicates a variation of 1.4% between chimpanzee and man and 5.1% between chimpanzee and rhesus monkey. The differences concerned single base changes. An Asp57 --> Asn mutation was detected in KIV-10; this residue is critical to the LBS of KIV-10 in human apo(a). To verify that the Asp57 --> Asn substitution was specific to apo(a), we have also cloned the cDNA-encoding plasminogen, which exhibited an Asp at the corresponding position in kringle IV. Using an in vitro binding assay, we have demonstrated that chimpanzee Lp(a) exhibits poor lysine-specific interaction with both intact and plasmin-degraded fibrin as compared to its human counterpart. We propose that the Asn57 substitution in KIV-10 of chimpanzee apo(a) is responsible for this property. Chimpanzee Lp(a) therefore represents an appropriate particle with which to explore the potential effects of Lp(a) on the fibrinolytic system, such as the inhibition of plasminogen activation or inhibition of t-PA activity.